The exposome can be characterized as the cumulative measure of all environmental exposures and associated biological responses over the entire life span. Environmental metabolomics has critical relevance for understanding the link between environmental pollution and human health and disease. The pollutants such as toxic metals and metalloids are related to industrial and agricultural activities, and induce stress responses, exhibiting characteristic changes. Untargeted metabolomics can identify exposure-related potential metabolite features through multiple LC-MS peaks. For this study, biological samples of pure control (n=35), abandoned mine exposure group (n=68), and refinery exposure group (n=118), were collected. Urinary and serum concentrations of exposure biomarkers Pb, Cd, Hg and As were increased in the high exposure group compared to the pure control group. We analyzed the changes in metabolites owing to long-term exposure to heavy metal in human plasma samples collected from environmentally vulnerable region such as refinery and abandoned mine area. As a result, we found several metabolites which show a significant difference among groups, such as C18 (Plasm) 22:6 PE, Arachidonic acid, DHA, EPA, etc. We performed ROC analysis to evaluate the possibility as a biomarker. Therefore, these results reflect that pollutants from environment vulnerable region might be associated with hypertension, ROS sensitivity and respiratory disease.